Targeted next-generation sequencing for the genetic diagnosis of dysferlinopathy

Ha Young Shin, Hoon Jang, Joo Hyung Han, Hyung Jun Park, Jung Hwan Lee, So Won Kim, Seung Min Kim, Young Eun Park, Dae Seong Kim, Duhee Bang, Min Goo Lee, Ji Hyun Lee, Young Chul Choi

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4 Citations (Scopus)


Dysferlinopathy comprises a group of autosomal recessive muscular dystrophies caused by mutations in the DYSF gene. Due to the large size of the gene and its lack of mutational hot spots, analysis of the DYSF gene is time-consuming and laborious using conventional sequencing methods. By next-generation sequencing (NGS), DYSF gene analysis has previously been validated through its incorporation in multi-gene panels or exome analyses. However, individual validation of NGS approaches for DYSF gene has not been performed. Here, we established and validated a hybridization capture-based target-enrichment followed by next-generation sequencing to detect mutations in patients with dysferlinopathy. With this approach, mean depth of coverage was approximately 450 fold and almost all (99.3%) of the targeted region had sequence coverage greater than 20 fold. When this approach was tested on samples from patients with known DYSF mutations, all known mutations were correctly retrieved. Using this method on 32 consecutive patient samples with dysferlinopathy, at least two pathogenic variants were detected in 28 (87.5%) samples and at least one pathogenic variant was identified in all samples. Our results suggested that the NGS-based screening method could facilitate efficient and accurate genetic diagnosis of dysferlinopathy.

Original languageEnglish
Pages (from-to)502-510
Number of pages9
JournalNeuromuscular Disorders
Issue number6
Publication statusPublished - 2015 Jun 1

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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    Shin, H. Y., Jang, H., Han, J. H., Park, H. J., Lee, J. H., Kim, S. W., Kim, S. M., Park, Y. E., Kim, D. S., Bang, D., Lee, M. G., Lee, J. H., & Choi, Y. C. (2015). Targeted next-generation sequencing for the genetic diagnosis of dysferlinopathy. Neuromuscular Disorders, 25(6), 502-510.